A role for the IgH intronic enhancer Eμ in enforcing allelic exclusion

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Abstract
The intronic enhancer (Eμ) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine Eμ's subsequent functions, we created an Igh allele with assembled VH gene but with Eμ removed. In mice homozygous for this Eμ-deficient allele, B cell development was normal and indistinguishable from that of mice with the same VH knockin and Eμ intact. In mice heterozygous for the Eμ-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for Eμ in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.